The present invention relates to a method for producing elastic vesicles and, more particularly, to a method for producing elastic vesicles for enveloping active ingredients of cosmetics.
Active ingredients with alleged special effects have been added into formulations as the techniques of skin care products evolve. However, it is still a problem whether these active ingredients can successfully enter the deep layers of human skin and act in the target area. Transdermal drug delivery systems are techniques permitting a drug to penetrate the skin to achieve effective concentration, which, when applied in development of cosmetics, can increase the penetrating speed and amount of the active ingredients of the skin care products. Commonly used methods include sonophoresis, iontophoresis, and vesicle enveloping technique. A liposome is one of vesicles and is a micro particle comprised of phospholipids. Since phospholipids are amphipathic molecules that will self-assembly into an aggregate when they reach the critical micellar concentration (CMC) in a polar solvent having a better hydrophilicity, and phospholipids have a lipid bilayer to effectively envelope the active ingredients while possessing excellent biofilm permeability. Thus, they are widely used in a vesicle enveloping technique. This technique was found in 1965 by Alec Bangham of Babraham Institute. Liposomes were for the first time accepted as vesicles for drugs in 1970, and animal tests were conducted. Amphotericin B (a liposome drug) was accepted to cure general fungal infection in Ireland in 1990. In 1995, the Food and Drug Administration of the U.S. approved Liposomal Doxorubicin to the market.
Research showed that liposomes are compatible with skin and tissues without causing allergy. Furthermore, liposomes can degrade into phospholipids and turn into a portion of the cell membrane. However, liposomes have two drawbacks. Firstly, liposomes have a large diameter and, thus, can only act on the upper layer of the corneum rather than penetrating the granular layer of the epidermis, leading to an increase in the amount of the active ingredients stagnant on the skin and, hence, failing to achieve effective absorption. Secondly, both research of Kirjavainen in 1999 and research of Fang et al. in 2001 showed that the active ingredients are less impotent in penetrating the skin when the structure of the liposome is more stable. According to the previous research results, liposomes lack elasticity and, thus, cannot penetrate the gap in the epidermal layer because the lipid bilayer structure is rigid.
Elastic vesicles, which are a special liquid transdermal drug vesicle and are different from conventional liposomes, were published in early 1990 for the first time. Elastic vesicles essentially consists of phosphatidylcholine (PC) and edge activators (EA). Phosphatidylcholine is the essential component of the vesicle. The edge activators provide the lipid bilayer membranes of the elastic vesicles with flexibility during production of the elastic vesicles.
Phosphatidylcholine is the essential component of a biofilm and consists of a hydrophilic polar head group formed by phosphoryl groups and two hydrophobic fatty acid chains. When the molecules of phospholipids disperse in water, the molecules self-assemble into a concentric ball structure due to the difference in the hydrophilicity and hydrophobicity at two ends. The water soluble substances are enveloped, and the fat soluble substances are embedded on the surfaces of the elastic vesicles. Edge activators, also referred to as “surfactants”, include both hydrophilicity and lipophilicity. The lipophilic groups generally consist of long-chain hydrocarbon radicals having small structural differences. There are more types of hydrophilic groups and, thus, having larger differences therebetween. Generally, single-chain surfactants having larger radiuses of curvatures are selected for the purpose of increasing the flowability in the lipid bilayer to improve the deformability and permeability, such that the elastic vesicles are highly deformable to penetrate through skin pores having a size much smaller than the elastic vesicles. Thus, the release of drugs can be prolonged, and the activity of the drugs can be enhanced through transdermal penetration.
Elastic vesicles can be applied in various drugs, including non-steroidal anti-inflammatory drugs, analgesics, insulin, anaesthetics, anti-malarial drugs, anti-cancer drugs, and melatonin. Elastic vesicles are suitable to hydrophilic and lipophilic drugs and possess biocompatibility and biodegradability. Since the structure of elastic vesicles is similar to that of natural phospholipids, the elastic vesicles can effectively prolong the release of drugs and reduce the half-life of drugs. Thus, it is a drug administration system worth developing. However, research of application of the elastic vesicles in the cosmetic field are few. If the elastic vesicles are applied to envelope the active ingredients, it will be a novel, promising technique.
However, production of elastic vesicles requires addition of organic solvents, and the safety of production is questioned. As an example, the research result published by Cevc and Blume in 1992 showed that preparation of elastic vesicles required dissolving phosphatidylcholine and edge activators with chloroform and methyl alcohol (which are organic solvents) at a ratio of 2:1, and the organic solvents were subsequently removed by rotary evaporation. However, residue of the organic solvents was still possible.